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Cebix Inc's presentation given by James Callaway, COO and President of Research and Development at the 46th Annual Meeting of the European Association for the Study of Diabetes in Stockholm, 20 – 24 September 2010. For more information about CEBIX please visit: http://www.Cebix.com For more information about EASD please see: http://www.easd2010.com/
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1 CONFIDENTIAL
Development of a once-‐weekly C-‐pep<de product
Disclosure
• James Callaway is an employee and shareholder of Cebix Incorporated
An agent for the treatment of mild to moderate peripheral neuropathy in type 1 diabetes
The therapy of choice in the treatment of this significant unmet medical need, based on improvement of sensory function
Initial Target Indication
3
Product Profile
Restores Sensory Nerve Conduc<on
Ekberg et al, Diabetes 2003
50
52
54
56
Baseline 6 wks 12 wks
SCV (m/s) C-‐pep<de n=26 Placebo n=23
Healthy Controls
p<0.05
Required 4 subcutaneous doses per day
5
Drug Product Development
Unmet medical need
Biology -‐ Func<on and Pathophysiology Safety Efficacy
Dose -‐ Replacement
Drug manufacturing
Regulatory Path End Points Drug delivery
Formula<on Criteria
6
Product load >1% of volume
1 2 3 4 5 6 7
Syringeability ≤ 27 gauge
< 20 seconds
<20% drug loss in burst PK profile consistent with
once weekly dosing
Selected Formula<on Technologies
7
PROMAXX Atrigel Pumps
Trans-‐ dermal patch
Alkermes
Octoplus
Eryto-‐ pharm
Halozyme
Altus
Alkamer
Nektar
Enzon
Syringability ≤ 27 gauge
Stable for > 1.5 years at 4°C
PK profile consistent with once weekly dosing
No more than 20 percent drug loss in burst
Product load of at least 1 percent of volume
Winning Formula<ons
Slow Release PK Profile (Dog)
Lot 1
Lot 2
Aqu
C-‐pe
p<de
con
c (ng/ml)
C-‐pe
p<de
con
c (ng/ml)
Depot Characteris<cs
• Approximates 7 day coverage
• 2-‐Log span spread from Cmax to Cmin
• Volume of injec<on less than 1 mL
• Viscosity keeps injec<on above 20 second target
Extended half-‐life
Extended Half-‐life PK profile (monkey)
12
Linear scale
60
100
40
20
0
C-‐pe
p<de
con
c (ng/ml)
0 4 8 12
Time (days)
Semi-‐logarithmic scale
100
1
10
C-‐pe
p<de
con
c (ng/ml)
0 4 8 12 16 16
Time (days)
T1/2 = 3 days
Extended Half-‐life or Depot
Half-‐life • Chemically altered • Ideal PK profile • Ideal Presenta<on
– like water – 31 G
• Excellent Tolerability • Manufacturing
– Simple
Depot • Natural C-‐pep<de • PK Profile not op<mal
– Exceeding Cmax by a Log
• Presenta<on – Ajrac<ve – Injectability acceptable
• Acceptable tolerability • Manufacturing
– Unknown risk
Long-‐Ac(ng-‐CP
CP
0
5
10
15
20
25
0 0.5 1 3 10 100
CP/Long-‐Ac(ng -‐CP [nmol/L]
pERK
1/2 [AU]
LA-‐CP CP
n=6-‐8
Chibalin lab at Karolinska: HEK-‐293 cells
ERK1/2 phosphoryla(on CP versus Long-‐Ac(ng CP
Regulatory & Clinical
Path Forward
Pre-‐IND Mee<ng with FDA July 2010
• Regulatory – FDA Confirmed qualifica<on of Subpart H
• Allows use of surrogate end point for Pivotal Phase 2b
• Clinical – Nerve conduc<on velocity accepted as the sole primary endpoint for approval
• Nonclinical – IND-‐enabling tox plan endorsed by FDA
16
FDA
Road to the Clinic
17 pre-‐IND mee<ng
Acute monkey tox In life Analysis
Human PK study IND submission
Acute rodent tox In life Analysis
Formula<ons screen
Qualify analy<cal methods (DS)
Methods create/approve (DP)
Fill prep Batch records
Fill
6-‐month rodent tox
6-‐month monkey tox
DS Process Development
Tox supplies
Develop &
Dec Jan Feb Mar
2010 2011
Apr May Jun Jul Aug Oct Nov Sep
DS Manufacturing
2011
Cebix Development Program 2012
18
2014 2013 2015 2010
Formula<on
Pre-‐clinical
6-‐mo interim data: surrogate marker
NDA submission
12-‐mo data: clinical end-‐point
Phase 2b NEUROPATHY
Confirm surrogate marker
Phase 3 NEUROPATHY
Human PK
Summary
• Clear biological ra<onale for C-‐pep<de replacement
• Company set Target Product Profile for pa<ent to have a once weekly “insulin-‐like experience”
• Established long-‐ac<ng C-‐pep<de which met the profile – Biological ac<vity confirmed in 3 separate models – Patents have been filed
• Full development program ini<ated
